Single DermaVir immunization: dose-dependent expansion of precursor/memory T cells against all HIV antigens in HIV-1 infected individuals

The GIHU004 study was designed to evaluate the safety and immunogenicity of three doses of DermaVir immunization in HIV-infected subjects on fully suppressive combination antiretroviral therapy (cART). This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted...

Full description

Saved in:

Bibliographic Details
Published in:	PloS one Vol. 7; no. 5; p. e35416
Main Authors:	Lisziewicz, Julianna, Bakare, Nyasha, Calarota, Sandra A, Bánhegyi, Dénes, Szlávik, János, Ujhelyi, Eszter, Tőke, Enikő R, Molnár, Levente, Lisziewicz, Zsolt, Autran, Brigitte, Lori, Franco
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 09-05-2012 Public Library of Science (PLoS)
Subjects:	Acquired immune deficiency syndrome Adolescent Adult AIDS AIDS vaccines AIDS Vaccines - administration & dosage AIDS Vaccines - immunology Antigen-antibody reactions Antigens Antigens, Viral - immunology Antiretroviral agents Antiretroviral drugs Antiretroviral therapy Biology CD4 antigen CD4-Positive T-Lymphocytes - immunology CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell proliferation Cohort Studies Deoxyribonucleic acid DNA Dosage Dose-Response Relationship, Immunologic Drainage measurement Epidermis Epidermis - immunology Female Follow-Up Studies Health aspects Highly active antiretroviral therapy HIV HIV antigens HIV Infections - immunology HIV Infections - therapy HIV-1 - immunology Human immunodeficiency virus Humans Immunization Immunogenicity Immunologic Memory Immunological memory Interferon Interferon-gamma - immunology Interleukin 2 Langerhans cells Langerhans Cells - immunology Lymph nodes Lymph Nodes - immunology Lymphocytes Lymphocytes T Male Medicine Memory cells Middle Aged Precursors Safety Side effects T cells Tat protein Vaccines Viral proteins Hungary United States > US Virginia Massachusetts
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	The GIHU004 study was designed to evaluate the safety and immunogenicity of three doses of DermaVir immunization in HIV-infected subjects on fully suppressive combination antiretroviral therapy (cART). This first-in-human dose escalation study was conducted with three topical DermaVir doses targeted to epidermal Langerhans cells to express fifteen HIV antigens in draining lymph nodes: 0.1 mg DNA targeted to two, 0.4 mg and 0.8 mg DNA targeted to four lymph nodes. Particularly, in the medium dose cohort 0.1 mg DNA was targeted per draining lymph node via ∼8 million Langerhans cells located in 80 cm(2) epidermis area. The 28-days study with 48-week safety follow-up evaluated HIV-specific T cell responses against Gag p17, Gag p24 and Gag p15, Tat and Rev antigens. DermaVir-associated side effects were mild, transient and not dose-dependent. Boosting of HIV-specific effector CD4(+) and CD8(+) T cells expressing IFN-gamma and IL-2 was detected against several antigens in every subject of the medium dose cohort. The striking result was the dose-dependent expansion of HIV-specific precursor/memory T cells with high proliferation capacity. In low, medium and high dose cohorts this HIV-specific T cell population increased by 325-, 136,202 and 50,759 counts after 4 weeks, and by 3,899, 9,878 and 18,382 counts after one year, respectively, compared to baseline. Single immunization with the DermaVir candidate therapeutic vaccine was safe and immunogenic in HIV-infected individuals. Based on the potent induction of Gag, Tat and Rev-specific memory T cells, especially in the medium dose cohort, we speculate that DermaVir boost T cell responses specific to all the 15 HIV antigens expressed from the single DNA. For durable immune reactivity repeated DermaVir immunization might be required since the frequency of DermaVir-boosted HIV-specific memory T cells decreased during the 48-week follow up. ClinicalTrial.gov NCT00712530.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: JL FL NB. Performed the experiments: SAC DB JS EU BA. Analyzed the data: LM ZL JL FL NB BA. Contributed reagents/materials/analysis tools: BA EU SAC. Wrote the paper: JL ERT.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0035416